脑膜炎球菌结合疫苗制备过程中各阶段产物的细菌内毒素含量分析

Assay of bacterial endotoxin in meningococcal conjugate vaccines during different preparation stages

目的:以细菌内毒素检查法(动态浊度法)对脑膜炎球菌结合疫苗生产过程中各阶段产物进行细菌内毒素含量分析,观察疫苗生产过程细菌内毒素来源及其变化,为今后疫苗生产过程中细菌内毒素质量控制提供依据。方法:在对供试品处理和方法的标准化的基础上,以《中华人民共和国药典》2010年版三部所录动态浊度法对疫苗不同生产阶段的过程产物和疫苗成品进行全面监控。结果:影响脑膜炎球菌结合疫苗细菌内毒素含量的主要来源为原料多糖和载体蛋白质,疫苗制备过程可以很好控制细菌内毒素含量。结论:疫苗生产过程可以有效控制疫苗的细菌内毒素含量,降低疫苗中的细菌内毒素含量可从原料着手,对多糖和载体蛋白质纯化工艺改进,进而控制疫苗的细菌内毒素含量至更低水平以提高疫苗的安全性。

Objective： To analyze the origin and variation of bacterial endotoxin in meningococcal conjugate vaccines by determining its contents in the intermediate products at different manufacturing stages by bacterial endotoxin test, thus providing experiment basis for control of bacterial endotoxin. Methods： Bacterial endotoxin test included in Chinese Pharmacopoeia Volume Ⅲ（2010 Edition） was adopted to determine the contents of bacterial endotoxin in the intermediate and final products of meningococcal conjugate vaccines on the basis of sample dilution test and standardization of the method. Results ： The principal origins of bacterial endotoxin in meningococcal conjugate vaccines were the manufacturing materials, i.e. meningococcal polysaccharides or carrier proteins, and the content of bacterial endotoxin could be well controlled during the preparation process. Conclusion： The content of bacterial endotoxin in meningococcal conjugate vaccines may be efficiently restrained or even lowered during the production process by optimizing the purification techniques for both of meningococcal polysaccharide and carrier proteins in order to improve the safety of the vaccines.